反式二氢二醇环氧苯并芘诱发细胞p53基因的变化

The alterations of p53 gene in cells induced by anti-BPDE

目的 观察苯并(a)芘[B(a)P]代谢产物反式二氢二醇环氧苯并芘[anti 7,8, dihydrodiol 9,10 epoxidebenzo(a)pyrene ,BPDE]诱发的恶性转化的人支气管上皮细胞(humanbronchialepithelialcells ,HBE)及其裸鼠成瘤细胞中的p5 3基因突变情况,探讨BPDE诱导细胞癌变的机制。方法 多聚酶链聚合反应 单链构象多态性分析(PCR SSCP)、基因测序。结果 PCR SSCP分析结果提示,反式BPDE诱发的恶性转化细胞及其裸鼠成瘤细胞p5 3基因的Exon 7和Exon 8有突变。基因测序发现裸鼠成瘤细胞(B3 )的p5 3基因Exon 8的第2 82位密码子位置出现了一个G→T点突变,其编码的氨基酸由精氨酸(CGG)→亮氨酸(CTG)。结论 反式BPDE可诱导p5 3基因发生突变,提示p5 3基因突变可能是BPDE诱导细胞癌变的重要机制之一。

Objective To study the alterations of p53 gene in the transformed human bronchial epithelia(HBE) cells induced by anti-7,8-dihydrodiol-9,10-epoxide benzo(a)pyrene (BPDE) the metabolite of benzo(a) pyrene and the tumor cells of naked rat developed from the transformed HBE cells.Methods Polymerase chain reaction-single strand confirmation polymorphism (PCR-SSCP),sequening.Results PCR-SSCP assay indicated that there were mutations in the p53 gene Exon 7 of B2,B3 cells and exon8 of B1,B2,B3 cells.Sequence analysis confirmed that there was a G→T point mutation at 282 condon in the p53 gene exon8 of B3 cells.the normal amino arginine was replaced by leucine.Conclusion Anti-BPDE can induce p53 gene mutations among the mutation hot spot of exon 5-exon 8,which indicates that in the process of anti-BPDE carcinogenesis the p53 gene acts an important role.